Genomic Uniformed-Screening Against Rare Disease In All Newborns (GUARDIAN)

The goal of this study is to learn how genomic sequencing technology can be used to effectively expand the conditions screened on newborn screening. Newborn screening ensures equity and allows all babies to have the same chance at the healthiest life. Families will be invited to have their newborn baby screened for additional conditions beyond what all babies are screened for as part of the newborn screening public health program. Families can choose to be part of the study or choose not to be part of the study and just have the routine newborn screening test. Families will also be able to choose to learn about their baby's risk for conditions that have effective treatments available but are not on the routine newborn screening panel or also learn about conditions for which there is not currently FDA approved medications but for which medications are under development or for which early intervention services or treatment of seizures may improve the child's outcome. Families will be invited to the study shortly after the baby is born and will learn the decision not to participate, and we will interview a subset of parents who agree to be interviewed. Newborns who screen positive will be referred to appropriate providers for care and will be followed through review of electronic medical records and parental follow up via phone, text, postal mail or email.

Study Overview

• Status: Recruiting
• Conditions: Early Onset Genetic Conditions With Near Complete Penetrance
• Intervention / Treatment: Other: Genome sequencing-based newborn screening

Detailed Description

Newborn screening (NBS) is the process of screening all newborns for select conditions shortly after birth. This process reduces morbidity and mortality by the detection of medically actionable conditions in pre-symptomatic newborns. Approximately 1 in every 180 newborns is diagnosed with a condition through NBS. NBS is a public health service; every infant regardless of health insurance or ability to pay is tested. NBS ensures equity and allows all babies to have the same chance at the healthiest life. Effective NBS requires coordination and collaboration from multiple stakeholders - the parents, the hospital of birth, state department of health lab, the pediatrician, and the specialty referral center.

Conditions included on the NBS must fulfill several criteria: 1) significant clinical benefit for the newborn early in life including treatment administered within the first few years of life, 2) readiness of public health departments to effectively screen for the condition, and 3) feasibility of successful implementation of population screening. In the United States, screening of newborns is under the purview of state public health departments. Each state decides which disorders to screen, and expansions to each state's panel of screened conditions. The federal government also plays a role through the Secretary of Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC). With rapid improvements in screening technology, diagnostic testing, and treatments, conditions not previously screened through NBS are being considered. Expanding NBS through genome-wide sequencing (GS) will be the most flexible and cost-effective way to add to what is currently in use.

• Study Type: Interventional
• Enrollment (Estimated): 100000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anah Hetzler; Phone Number: 212-305-5508; Email: ak3578@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center/NYP
      • Principal Investigator: Rudolph Leibel, MD
      • Contact: Anah Hetzler; Phone Number: 212-305-5508; Email: ak3578@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 month (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newborns admitted to the well-baby nurseries from the recruiting hospitals
• Newborns born after 33 weeks of gestation
• Newborns whose parents are English, Mandarin, or Spanish speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enrolled in the study; All newborns enrolled in the study will be evaluated.	Other: Genome sequencing-based newborn screening; Dried blood spots collected at birth for routine newborn screening will be used for genome sequencing based screening of a defined set of conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enrollment Rate (percentage)	Enrollment rate will be defined as: number of enrolled newborns / number of newborns approached by the research assistant.	From study launch to end of enrollment (up to 5 years)
Successful Sequencing Rate (percentage)	Successful sequencing rate will be defined as: number of successful sequencing / number of enrolled newborns.	Up to 6 months after the end of enrollment
Screen Positive Rate (percentage)	Screen positive rate will be defined as: number of newborns with a positive screening / number of successful sequencing.	Up to 6 months after the end of enrollment
True Positive Rate (percentage)	True positive rate will be defined as: number of confirmed diagnosis / number of screen positive.	Up to 6 months after the end of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on Decision Regret Scale	The Decision Regret Scale measures distress or remorse after a health care decision. This 5-items scale ranges from 0 (no regrets - best outcome) to 100 (highest regret - worst outcome). Scores above 1 and below 25 are considered as an indication of mild regret. Scores above 25 are considered as an indication of moderate to severe regret.	Up to 6 months after the end of enrollment

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: New York State Department of Health; Illumina, Inc.; GeneDx
• Investigators: Principal Investigator: Wendy K. Chung, MD, PhD, Boston Children's Hospital

Publications and helpful links

General Publications

• Ziegler A, Koval-Burt C, Kay DM, Suchy SF, Begtrup A, Langley KG, Hernan R, Amendola LM, Boyd BM, Bradley J, Brandt T, Cohen LL, Coffey AJ, Devaney JM, Dygulska B, Friedman B, Fuleihan RL, Gyimah A, Hahn S, Hofherr S, Hruska KS, Hu Z, Jeanne M, Jin G, Johnson DA, Kavus H, Leibel RL, Lobritto SJ, McGee S, Milner JD, McWalter K, Monaghan KG, Orange JS, Pimentel Soler N, Quevedo Y, Ratner S, Retterer K, Shah A, Shapiro N, Sicko RJ, Silver ES, Strom S, Torene RI, Williams O, Ustach VD, Wynn J, Taft RJ, Kruszka P, Caggana M, Chung WK. Expanded Newborn Screening Using Genome Sequencing for Early Actionable Conditions. JAMA. 2025 Jan 21;333(3):232-240. doi: 10.1001/jama.2024.19662.

Helpful Links

• <p>GUARDIAN Study Website</p>

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: August 4, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2026
• Last Update Submitted That Met QC Criteria: September 18, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Genome sequencing; Newborn screening
• Other Study ID Numbers: AAAS9161

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

IPD will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No